adenosine receptor antagonist combination therapy for metastatic castrate resistant prostate cancer

Conditions: Prostatic Neoplasms, Castration-Resistant; Androgen-Resistant Prostatic Neoplasms; Castration Resistant Prostatic Neoplasms; Prostatic Cancer, Castration-Resistant

Summary: this is a phase 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of etrumadenant (ab928)-based combination therapy in participants with metastatic castrate resistant prostate cancer (mcrpc).


Eligibility criteria:
general inclusion criteria: * male participants; age ≥ 18 years * metastatic castrate-resistant prostate cancer while on anti-androgen treatment with castrate levels of testosterone (≤1.7 nanomoles per liter \[nmol/l\] or 50 nanograms per deciliter \[ng/dl\]) * measurable or non-measurable disease as per radiographic evaluation * participants with measurable disease may require a fresh tumor biopsy at study entry * eastern cooperative oncology group (ecog) performance status of 0 or 1 * life expectancy of at least 3 months * adequate hematologic and end-organ function * human immunodeficiency virus (hiv), hepatitis b, and c test results negative prior to first study treatment inclusion criteria for participants receiving an enzalutamide-containing treatment * disease progression after prior treatment with abiraterone inclusion criteria for participants receiving a docetaxel-containing treatment * disease progression after prior androgen synthesis inhibitor therapy inclusion criteria for all other participants * disease progression after prior androgen synthesis inhibitor treatment and up to 2 prior lines of taxane chemotherapy general exclusion criteria: * prior treatment with immune checkpoint blockade therapy * prior anticancer treatment including approved agents, systemic radiotherapy, or investigational therapy, within 2-4 weeks prior first study treatment * corrected qt interval (qtc) ≥480 msec using fredericia's qt correction formula (based on an average of triplicate recordings) * prior allogeneic stem cell or solid organ transplantation * prior treatment with drugs that stimulate the immune system within 4 weeks prior to first study treatment * prior treatment with drugs that suppress the immune system within 2 weeks prior to first study treatment * received a live, attenuated vaccine within 4 weeks prior to first study treatment, or may need to receive a vaccine during study treatment * presence of metastases in the brain or cancer spreading into the cerebrospinal fluid - csf (leptomeningeal disease) * prior pulmonary fibrosis, pneumonia, or pneumonitis * cancer other than prostate within 2 years prior to study entry, except for some cancers with a low risk of spreading like non-melanoma skin * prior treatment with an agent targeting the adenosine pathway * no oral or iv antibiotics within 2 weeks prior to first study treatment * no severe infection within 4 weeks prior to first study treatment * no clinically significant cardiac disease * inability to swallow medications exclusion criteria for participants receiving an enzalutamide-containing treatment * prior treatment with docetaxel, cabazitaxel, or other taxane chemotherapy (prior docetaxel \[up to 6 cycles\] for hormone-sensitive prostate cancer is allowed if the last dose was at least 6 months prior to study treatment initiation) * prior treatment with enzalutamide or similar therapy other than abiraterone * active or history of autoimmune disease or immune deficiency * history of severe allergic reactions to antibody therapy * concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong cyp3a4 inducers and cyp3a4 inhibitors) within 4 weeks prior to and throughout study treatment exclusion criteria for participants receiving a docetaxel-containing treatment * prior treatment with docetaxel, cabazitaxel, or other taxane chemotherapy * active or history of autoimmune disease or immune deficiency * history of severe allergic reactions to antibody therapy * concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong cyp3a4 inducers and cyp3a4 inhibitors) within 4 weeks prior to and throughout study treatment exclusion criteria for all other participants * prior treatment with docetaxel, cabazitaxel, topoisomerase 1 inhibitors, or other taxane chemotherapy * active or history of autoimmune disease or immune deficiency * history of severe allergic reactions to antibody therapy * concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong cyp3a4 inducers and cyp3a4 inhibitors) within 4 weeks prior to and throughout study treatment